Recent advances in the field of structural biology and quantitative proteomics mean that there is now sufficient information available to allow the construction of meaningful, working molecular models of physiological environments. Such environmental models, when coupled to simulation methods that enable the dynamics of the systems to be modeled, will allow key biochemical processes such as protein folding and protein-protein association events to be observed in settings that much more closely mimic those encountered in real life. The project proposed here has two major objectives which will be pursued in parallel: (1) molecular simulation methods that have been under development in the PI's laboratory for some years will be extended and accelerated to make them suitable for use in simulating the dynamics of very large-scale macromolecular systems (e.g. comprising 10,000 macromolecules), (2) structural biological and quantitative proteomics data will be utilized to build preliminary 3D models of four different environments in the model prokaryote Escherichia coli: the cytoplasm, periplasm, and inner and outer-membranes